There are two components in this project and both are extended from our continuous commitment to the clinical investigation of viral hepatitis. One of these is an effort to respond to the increasing demand for a more precise measurement of relevant genomic information in any viral infection. The knowledge of the presence of specific viral gene will help in identifying the infectious agent. However, to assess the stage of a disease, to evaluate the efficacy of a treatment, to determine the value of a predictor in the progression of a disease and to monitor the patient?s disease progression, a more precise and quantitative analysis of the specific gene would be required. This previous research-oriented question can now begin to be answered in routine clinical laboratories with the advanced technology of molecular biology, such as polymerase chain reaction (PCR), and sequencing and mapping of the restriction nuclease digested fragments. We initiated developmental research in molecular diagnostic technology to meet our clinical study need for HBV, HCV, and HIV infection. Whenever possible, we would improve the basic PCR technique to become a semi-quantitative procedure. During the last 2 years, we were able to apply the same principles of using PCR as primary study tool for viral infection to several newly identified human hepatitis viruses or suspected hepatitis viruses such as HGV, TTV, and SENV. We found that these viruses were indeed transmissible by blood transfusion but have little or no impact on post-transfusion hepatitis. Although specific HGV RNA was identified in both recipients and paired donors sera, it could also be found in non-transfused controls. It could be found in patients with chronic infection with mild or no observed liver function abnormality but their causative relationship could not be determined. The prevalence of these viruses in blood donors, in general, was higher than that of HCV. The other part of this project is related to viral discovery. We have always maintained an effort to find other causative viral agents that may be responsible for hepatitis cases with unidentifiable cause. Due to its great resource requirement, we tried to conduct this project with industry partners under CRADA. We divided responsibilities by concentrating our group in confirming initial discovery and clinical characterization. In the past few years, we also engaged in developing cloning techniques for rare event genes that might identify low copy infectious agents from patient sera or tissues. The techniques developed were unique and with the potential to be applied to a large number of specimens at the same time. An invention report has been filed with the NIH technology transfer office and is being considered for possible patent application.